Journal of Alzheimer's Disease - Volume 88, issue 4

Authors: Krishnadas, Natasha | Huang, Kun | Schultz, Stephanie A. | Doré, Vincent | Bourgeat, Pierrick | Goh, Anita M.Y. | Lamb, Fiona | Bozinovski, Svetlana | Burnham, Samantha C. | Robertson, Joanne S. | Laws, Simon M. | Maruff, Paul | Masters, Colin L. | Villemagne, Victor L. | Rowe, Christopher C.

Article Type: Research Article

Abstract: Background: In Alzheimer’s disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice. Objective: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using 18 F-MK6240, and whether these patterns are associated with different demographic and cognitive profiles. Methods: Tau 18 F-MK6240 PET images of 151 amyloid-β positive participants with mild cognitive impairment (MCI) and dementia were visually rated …as: tau negative, limbic predominant (LP), MTL-sparing, and Typical by two readers. Groups were evaluated for differences in age, APOE ɛ4 carriage, hippocampal volumes, and cognition (MMSE, composite memory and non-memory scores). Voxel-wise contrasts were also performed. Results: Visual rating resulted in 59.6% classified as Typical, 17.9% as MTL-sparing, 9.9% LP, and 12.6% as tau negative. Intra-rater and inter-rater reliability was strong (Cohen’s kappa values of 0.89 and 0.86 respectively). Tracer retention in a “hook”-like distribution on sagittal sequences was observed in the LP and Typical groups. The visually classified MTL-sparing group had lower APOE ɛ4 carriage and relatively preserved hippocampal volumes. Higher MTL tau was associated with greater amnestic cognitive impairment. High cortical tau was associated with greater impairments on non-memory domains of cognition, and individuals with high cortical tau were more likely to have dementia than MCI. Conclusion: Tau distribution patterns can be visually identified using 18 F-MK6240 PET and are associated with differences in APOE ɛ4 carriage, hippocampal volumes, and cognition. Show more

Keywords: Alzheimer’s disease, cognition, 18F-MK6240, patterns, positron emission tomography, tau

DOI: 10.3233/JAD-215558

Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1627-1637, 2022

Authors: Xue, Chuanwei | Tang, Yi | Wang, Changming | Yang, Haibo | Li, Liang

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) has been confirmed as an influencing factor of visual impairment, but potential concomitant effects on visual and cognitive performance are not well understood. Objective: To provide a new method for early screening of Alzheimer’s disease and further explore the theoretical mechanism of the decline of whole visual and cognitive performance in AD. Methods: We studied 60 individuals without dementia as normal control (NC), 74 individuals with subjective cognitive decline (SCD), 60 individuals with amnesia mild cognitive impairment (aMCI), and 75 patients with AD on a battery of tests designed to measure multiple …aspects of basic and higher-order visual perception and cognition. All subjects performed on same visual and cognitive test batteries. Results: The results showed both of four groups, with the stimulus-presentation time being longer, the visual-search performance improved, and both the eye interest-area first fixation duration and the interest-area-fixation count increased. Particularly under the noise-masking condition, the AD group performed the worst at stimulus-presentation times between 300 and 900 ms. The aMCI group, but not the SCD group, performed worse than the NC group at the stimulus-presentation time of either 300 or 500 ms. The interest-area-fixation count was higher in all the patient groups than that in the NC group, and distinguishable between participants with AD and those with SCD or aMCI. Conclusion: The visual-search performance combined with eye-movement tracking under the noise-masking condition can be used for distinguishing AD from normal aging, SCD, and aMCI. Show more

Keywords: Alzheimer’s disease, attention allocation, cognitive load, eye movement tracking, visual search

DOI: 10.3233/JAD-220209

Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1639-1650, 2022

Authors: Terracciano, Antonio | Piras, Maria Rita | Sutin, Angelina R. | Delitala, Alessandro | Curreli, Nicolò Camillo | Balaci, Lenuta | Marongiu, Michele | Zhu, Xianghe | Aschwanden, Damaris | Luchetti, Martina | Oppong, Richard | Schlessinger, David | Cucca, Francesco | Launer, Lenore J. | Fiorillo, Edoardo

Article Type: Research Article

Abstract: Background: Few studies have examined the associations between personality facets and dementia risk and rarely included individuals from rural settings or with low education. Objective: To examine the association between personality and the risk of cognitive impairment. Methods: Participants (N = 1,668; age 50 to 94 at baseline; 56.4% women; 86.5% less than high school diploma) were from a rural region of Sardinia (Italy) who completed the Revised NEO Personality Inventory (NEO-PI-R) during the first wave (2001–2004) and the Mini-Mental State Examination (MMSE) at waves two to five (2005–2021). Cox regression was used to test personality and covariates …as predictors of cognitive impairment based on MMSE education-adjusted cutoffs. Results: During the up to 18-year follow-up (M = 10.38; SD = 4.76), 187 individuals (11.2%) scored as cognitively impaired. Participants with higher neuroticism (particularly the depression facet [HR = 1.22, 95% CI = 1.06–1.40]), and lower agreeableness (particularly the modesty facet [HR = 0.83, 95% CI = 0.71–0.97]) and lower conscientiousness (particularly the dutifulness facet [HR = 0.78, 95% CI = 0.67–0.92]) were at higher risk of cognitive impairment. Lower warmth ([HR = 0.75, 95% CI = 0.65–0.87], facet of extraversion) and ideas ([HR = 0.76, 95% CI = 0.65–0.89], facet of openness) were also associated with increased risk of impairment. These associations were virtually unchanged in models that accounted for other risk factors, including smoking, depression, obesity, hypertension, diabetes, and apolipoprotein E (APOE ) ɛ4 carrier status. Across the five domains, sex and the APOE variant did not moderate the associations. Conclusion: In a sample with demographic characteristics underrepresented in dementia research, this study identifies personality domains and facets most relevant to the risk of cognitive impairment. Show more

Keywords: Cognition, dementia, longitudinal study, personality, risk factors

DOI: 10.3233/JAD-220400

Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1651-1661, 2022

Authors: Polcher, Alexandra | Wolfsgruber, Steffen | Peters, Oliver | Frölich, Lutz | Wiltfang, Jens | Kornhuber, Johannes | Hüll, Michael | Rüther, Eckart | Lewczuk, Piotr | Maier, Wolfgang | Jessen, Frank | Wagner, Michael

Article Type: Research Article

Abstract: Background: Consideration of many tests from different cognitive domains in defining mild cognitive impairment (MCI) is clinical routine, but guidelines for a neuropsychological operationalization of MCI are lacking. Objective: Among different operational MCI criteria, to identify those which are best in predicting either conversion to dementia, or a biomarker profile indicative for Alzheimer’s disease (AD). Methods: Memory clinic patients without dementia (N  = 558; mean age = 66; up to 3 years of follow-up; n  = 360 with baseline CSF biomarkers) were included in an observational study using most liberal criteria of cognitive impairment. Four operational definitions of MCI were …retrospectively applied: 1) amnestic MCI (CERAD word list delayed recall), 2) CERAD total score, 3) comprehensive criteria and 4) base rate corrected CERAD. We compared their accuracy in predicting incident all-cause dementia or AD dementia within three years, or a concurrent CSF Aβ42 /tau-ratio indicative of AD. Results: The four definitions overlapped considerably, classified 35–58% of the original sample as impaired and were associated with markedly increased PPVs regarding incident all-cause dementia (39–46% versus 26% of the original sample), AD dementia and AD biomarker positivity. The base rate corrected MCI definition had the highest prognostic accuracy. Conclusion: he operational criteria examined seem suitable to specify MCI in memory clinic settings, as they identify subjects at high risk of clinical progression. Depending on the neuropsychological battery in use, one or several of these criteria could help to calibrate the clinical judgment of test results, reduce false-positive decisions, and define risk-enriched groups for clinical trials. Show more

Keywords: Alzheimer’s disease, biomarker, cognition, conversion, dementia, diagnosis, DSM-5 mild NCD, mild cognitive impairment, prognosis

DOI: 10.3233/JAD-215548

Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1663-1678, 2022